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Physalin B induces G2/M cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by altering mitochondrial function

Cao, Conga; Zhu, Linga; Chen, Yea,c; Wang, Cheng-Huic; ShenTu, Jian-zhongb; Zheng, Yun-Liangb

doi: 10.1097/CAD.0000000000000701
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Physalin B (PB) is one of the major constituents of Physalis alkekengi var. franchetii, a well-known Chinese traditional herb. In this study, we demonstrated for the first time that PB exhibits significant antiproliferative and apoptotic activity in A549 human lung cancer cells in a concentration-dependent and time-dependent manner. Flow cytometric analyses indicated that PB-induced G2/M arrest through down-regulation of cyclin B1 and cell division control protein cyclin-dependent kinase 1, and up-regulation of p21. The reduction in the level of cyclin B1/cyclin-dependent kinase 1 complex down-regulated oxidative phosphorylation multisubunit activity to reduce mitochondrial energetic homeostasis. Moreover, defects in mitochondrial ATP synthesis and mitochondrial membrane potential were found in PB-treated cell lines. These abnormalities led to an increase in intracellular superoxide and apoptosis. Thus, as an inhibitor of mitochondrial energetic homeostasis, PB demonstrates potent antitumor activities and may be developed as an alternative therapeutic agent against non-small-cell lung cancer.

aThe Children’s Hospital

bState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Research Center for Clinical Pharmacy, The First Affiliated Hospital

cDepartment of Genetics, Institute of Genetics, Zhejiang University, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China

Correspondence to Dr Yun-Liang Zheng, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, People’s Republic of China Tel: +86 571 8723 6537; fax: +86 571 8723 6560; e-mail: ylzheng1984@zju.edu.cn

Received April 7, 2018

Accepted September 17, 2018

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